Atlas of Clinical Hematology - part 8 potx

V Fig. 135 a – d. Lymph node hyperplasia a Two immunoblasts and an eosinophil in lower half of field b Plasmablast at top center, several plasma cells at bottom, tissue basophil at left c Starry sky macrophage at center, several immunoblasts at right d Immunoblast at upper left, above it a centroblast, at right a reticulum cell 301 6 · Cytology of Lymph Node and Splenic Aspirates V Fig. 136 a – d. Lymph node hyperplasia in toxoplasmosis a Epitheloid cell lymphadenitis (Piringer- Kuchinka type). Epitheloid cell cluster at left, an immunoblast at center, to its right a binucleated plasma cell b Starry sky macrophage at center c Starry sky macrophage. Typical speci- men with many coarse granular inclu- sions and cytoplasmic vacuoles d Epitheloid cell shows typical fine but dense chromatin pattern with one or two blue, sharply defined nucleoli 302 Chapter V · Lymph Nodes and Spleen V Fig. 137 a, b. Tuberculous lymphade- nitis a Langhans giant cell b Syncytium of epitheloid cells Fig. 138 a, b. Sarcoidosis (Boeck disease), lymph node a Numerous epitheloid cells resembling a school of fish b Epitheloid cells in a “footprint” configuration 303 6 · Cytology of Lymph Node and Splenic Aspirates V 6.2 Infectious Mononucleosis Infectious mononucleosis is caused by the Ep- stein-Barr virus. Cytologically it is the prototype of lymph node hyperplasias of viral etiology. The clinical picture may be dominated by lymph node enlargement and splenomegaly or by a pseudo- membranous, lacunar, or ulcerative sore throat. Fever may reach 39 8C and persists for several days or as long as 2 to 3 weeks. Often the fever precedes the onset of glandular swelling. The red blood count is usually normal, and mild an- emia is rare. Generally there is a leukocytosis of 10,000 to 15,000/lL, which in rare cases exceeds 50,000/lL. Sporadic cases present with leukocy- topenia; this finding plus the pharyngitis can mi- mic agranulocytosis. Thrombocytopenia is occa- sionally seen and may be so pronounced that a hemorrhagic diathesis results. The leukocyte dis- tribution is characteristic. Examination of the blood smear shows a predominance of pleo- morphic mononucleated cells (60 %–90 %), which give the disease its name. Morphologically these cells may resemble young lymphocytes or lymphoblasts. In the early phase of the disease one finds granulated lymphocytes or lympho- cytes with small vacuoles at the circumference of the cytoplasm. Some appear as large blast- like cells with strongly basophilic cytoplasm. A significant increase in monocytes is not observed. Because similar cells can occur in other viral dis- eases, they have also been referred to as “viro- cytes” or lymphoid cells. The nuclei are pleo- morphic, often kidney-shaped or irregular, and the nuclear chromatin forms a coarse meshwork of loosely arranged strands. One or more nucleoli are usually present. Azurophilic granules are found in some cells, which represent transformed T-lymphocytes. Bone marrow findings are gener- ally nonspecific, and thus the changes are typical of infection. The mononuclear elements of the bone marrow may be increased in a few cases, but never to a high degree. By contrast, large numbers of typical cells are found in lymph node aspirates (Fig. 139). The pic- ture is dominated by mononuclear cells very si- milar or identical to those in the peripheral blood. Particularly striking are the large basophilic cells whose “transformed” state is evidenced by their enlarged, blue-tinged nucleoli. The cytologic changes can even cause confusion with Hodgkin cells (“Hodgkin-like cells”). Isolated epitheloid cells are also found. The diagnosis of infectious mononucleosis is established by detecting antibodies against the Epstein-Barr virus (EBV). While the rapid tests give a general impression as to whether infectious mononucleosis is present, their capabilities are otherwise limited. 304 Chapter V · Lymph Nodes and Spleen V Fig. 139 a – d. Infectious mononucleo- sis, lymph node a Marked increase of immunoblasts, macrophage at lower right b At center an immunoblast, several plasma cells c Various immunoblasts, with several pleomorphic lymphoid cells in lower half of field d Two strongly stimulated immuno- blasts, Hodgkin-like cells 305 6 · Cytology of Lymph Node and Splenic Aspirates V Fig. 140 a – d. Blood smears in infectious mononucleosis a–c Typic al pleomorphic lymphatic cells. Often these cells have irregular nuclear contours and basophilic cyto- plasm, an d some resemble bla sts b c d Detection of CD3, APAAP method. CD3 is detectable in the typical cells of in- fectious mononucleosis (red). These cells represent transformed T lymphocytes 306 Chapter V · Lymph Nodes and Spleen V 6.3 Persistent Polyclonal B Lymphocytosis This is a lymphocytosis stable for years, and bi- nucleated lymphocytes are detected in peripheral blood smears (about 3 %). These changes are almost only found in cigarette-smoking women under 50 years of age. In most cases there is a polyclonal increase of IgM; an association with HLA-DR 7 seems to exist. Of 25 women with this anomaly, 77 % had an isochromosome 3q(+i(3q)) (Fig. 140 e). Fig. 140 e. Lympho- cytes with two nuclei in persistent polyclo- nal B lymphocytosis 307 6 · Cytology of Lymph Node and Splenic Aspirates V 6.4 Maligne Non-Hodgkin-Lymphome und Hodgkin-Lymphom Wa¨hrend das Hodgkin-Lymphom ein eigenes Krankheitsbild (mit großer Var iationsbreite in Symptomatik und Prognose) darstellt, bildet die Gruppe der malignen Non-Hodgkin-Lym- phome eine hinsichtlich Erscheinungsbild, Prog- nose und Therapie recht heterogener Krankheits- gruppe, deren U ¨ bersichtlichkeit zudem durch die wechselnden Klassifizierungsvorschla¨ge noch zu- sa¨tzlich erschwert wird. Tabelle 14 und 15 geben einen U ¨ berblick u¨ber die Non-Hodgkin-Lym- phome. In Tab. 16 sind typische Immunmar- ker-Profile zusammengestellt. Nach der Herkunft der erkrankten Zellen ko¨n- nen B- und T-Zell-Lymphome unterschieden wer- den. B-Zell-Lymphome sind in Europa und Ame- rika ha¨ufiger, wa¨hrend die T-Zell-Lymphome in Asien u¨berwiegen. Unter Einbeziehung von mor- phologischen und zytochemischen Befunden, Im- munpha¨notyp, Zytogenetik und Molekulargene- tik sowie klinischen Daten hat die WHO-Arbeits- gruppe nach den Prinzipien der Revised Euro- pean-American Classification of Lymphoid Neo- plasms (REAL) die neue Einteilung der malignen Non-Hodgkin-Lymphome und verwandter Er- krankungen konzipiert. Nach wie vor stu¨tzt sich der Prima¨rbefund auf die Morphologie und manche Erkrankungen sind alleine morpho- logisch definiert, ha¨ufig ist aber die Definition einer Entita¨t ohne Immunpha¨notyp oder gene- tisch-molekulargenetisches Profil nicht mo¨glich. B-, T- und NK-Zell-Neoplasien werden weiter in Vorstufen-(Precursor) und reife (mature) Er- krankungen unterteilt. Auf die Einteilung nach prognostischen Kriterien (niedrig-maligne – in- dolent, intermedia¨r – aggressiv, hoch-maligne – sehr aggressiv) wurde verzichtet. Es ist nicht immer mo¨glich, allein mit Hilfe der Ausstrichzytologie eine eindeutige Klassifizie- rung der verschiedenen Lymphome vorzuneh- men. Trotzdem gibt es eine Reihe von zytomor- phologischen Kriterien, die in den meisten Fa¨llen zumindest eine Verdachtsdiagnos e gestatten. Sie sollen in den folgenden Abbildungen dargestellt werden. Die aktuelle Diagnostik und Klassifizierung der malignen NHL stu¨tzt sich auf die histologi- sche und immunologische Untersuchung von ex- stirpierten Lymphknoten oder anderen befalle- nen Geweben. Wie bei den akuten Leuka¨mien sind zytogenetische oder molekulargenetische Befunde wichtige Erga¨nzungen oder sogar ent- scheidend fu¨r die genaue Einordnung. Lymph- knotenpunktate spielen in der Prima¨rdiagnostik eine untergeordnete Rolle, es sei denn, periphere Lymphknoten ko¨nnen aus technischen Gru¨nden nicht exstirpiert werden. Andererseits ist die Punktatdiagnostik eine wichtige Erga¨nzung, wenn Organe im Abdomen, Thorax oder intraab- dominell gelegene Lymphknoten unter sonogra- phischer oder computertomographischer Kon- trolle gezielt punktiert werden ko¨nnen. Auch zur schnell eren Orientierung oder Verlaufskon- trolle sind sie hilfreich. In unterschiedlichem Gra- de ist auch das Knochenmark befallen, und/ oder es kommt zur leuka¨mischen Ausschwemmung in das periphere Blut. Wir werden in diesem Ab- schnitt auf die Beteiligung von Knochenmark und Blut bei NHL eingehen, im u¨brigen verweisen wir auf die Publikation zur WHO-Klassifizierung. Beim Hodgkin-Lymphom ist der Knochenmark- befall am ehesten nach histologischer Untersu- chung von Biopsien, selten auc h im Ausstrich von Aspiraten nachzuweisen. Das periphere Blut liefert nur indirekte Hinweise, wenn eine Lymphopenie oder selten eine Eosinophilie be- stehen. Wir richten uns bei der Nomenklatur nach der WHO-Klassifizierung. Bei der histologischen Beurteilung von Kno- chenmark-Schnittpra¨paraten spielt die Art des Infiltrationsmuster s speziell in den fru¨hen Sta- dien der Erkrankung eine wichtige Rolle, da es teilweise recht spezifisch ist. In der Schemazeichnung 1 ist die Topographie von Lymphominfiltraten im Knochenmark sche- matisch dargestellt (Schaefer, H. E.). 308 Kapitel V · Lymphknoten und Milz V Paratrabekular: Splenic marginal zone lympho- ma, mantle cell lymphoma Paratrabekular osteoclastic: Plasma cell myelo- ma, adult T-cell leukemia/lymphoma Random interstitial: Advanced hairy cell leuke- mia, large B-cell lymphoma Random tumorforming: Lar ge B-cell lymphoma, Hodgkin-lymphoma, advanced hairy cell leuke- mia Courtesy Prof. Dr. H. E. Schaefer, Freiburg. Up until now, he has only presented his schematic drawings publicly once previously, during a Japa- nese-Korean workshop in 1995. Suggested Further Reading World Health Organisation (2001) Classification of Tumours: Pathology and Genetics. IARC Press, Lyon (Tumou rs of Haematopoietic and Lym- phoid Tissues. Ed.: E. S. Jaffe, N. L. Harris, H. Stein, J. W. Vardiman) Table 14. WHO classification of mature B-cell neoplasms B-cell neoplasms Precursor B-cell neoplasm Precursor B lymphoblastic leukemia lymphoma Mature B-cell neoplasms Chronic lymphocytic leukemia / small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone lymphoma Hairy cel l leukemia Plasma cell myeloma Monoclonal gammopathy of undetermined significance (MGUS) Solitary plasmacytoma of bone Extraosseous plasmacytoma Primary amyloidosis Heavy chain diseases Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) Nodal marginal zone B-cell lymphoma Follicular lymphoma Mantle cel l lymphoma Diffuse large B-cell lymphoma Mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma Primary effusion lymphoma Burkitt lymphoma/leukemia B-cell proliferations of uncertain malignant potential Lymphomatoid granulomatosis Post-transplant lymphoproliferative disorder, polymorphic 309 6 · Cytology of Lymph Node and Splenic Aspirates V Table 15. Immune markers in leukemic forms of non-Hodgkin lymphoma Marker B-CLL B-PLL HCL FL MCL SLVL T-CLL / LGL SS T-PLL ATLL SIg (þ) þþ þþ þþ þþ þþ À À À À À CD2 ÀÀÀÀÀÀþþþþþ CD3 ÀÀÀÀÀÀþÀþþþ CD4 ÀÀÀÀÀÀÀÀþþ/ Àþ CD5 þþÀÀÀþÀÀÀþþþ CD7 ÀÀÀÀÀÀÀÀþ/ Àþ À/ þ CD8 ÀÀÀÀÀÀþþ/ Àþ/ Àþ/ Àþ/ À CD19 / 20 / 24 þþ þþ þþ þ þ þþ À À À À À CD22 þ / Àþþ þþ þ þ þþ À À À À À CD10 ÀÀÀþ/ ÀÀÀÀÀÀÀÀ CD25 ÀÀþþÀÀþ/ ÀÀ À À À þþ CD56 ÀÀÀÀÀÀÀþÀÀÀ CD103 ÀÀþþÀÀÀÀÀÀÀÀ HL-DR þþ þþ þþ þþ þþ þþ À À À À À À¼negative; (+) ¼ weakly positive; + ¼ positive; ++ ¼ markedly positive; +++ ¼ strongly positive; +/À¼majority of cases positive; À /+ ¼ majority of cases negative. CLL, chronic lymph ocytic leukemia; PLL, prolymphocytic leukemia; HCL, hairy cell leukemia; FL, follicular lymphoma; MCL, mantle cell lymphoma; SLVL, splenic lymphoma with villous lymphocytes; LGL, large granulated lymphocyte leukemia; SS, Se´zary syndrome; ATLL, adult T-cell leukemia/lymphoma 310 Chapter V · Lymph Nodes and Spleen [...]... autoantibodies) The depletion of normal B-lineage cells from the bone marrow and lymph nodes almost always produces an increasing hypogammaglobulinemia that may culminate in an antibody deficiency syndrome The lymphocytes of CLL have B-cell properties (B-CLL) in the majority of cases seen in Europe and America The existence of a T-CLL is controversial The mature-cell type of T-cell leukemia or NK-cell leukemia is... Hepatosplenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Nodal Angioimmunoblastic T-cell lymphoma Peripheral T-cell lymphoma, unspecified Anaplastic large cell lymphoma Neoplasm of uncertain lineage and stage of differentiation Blastic NK-cell lymphoma 1 Clinically not considered a neoplastic disorder V 336 Chapter V · Lymph Nodes and Spleen Figs 153 – 1 58 Mature lymphomas of T-cell lineage... shows weakly diffuse and polar-cap patterns of activity V f Immunocytochemical detection of CD11c g Immunocytochemical detection of CD103 APAAP technique 327 6 · Cytology of Lymph Node and Splenic Aspirates Fig 148a – d Variant of hairy cell leukemia (HCL-V) This is another B-lineage form, usually associated with marked leukocytosis The nuclear structure resembles that of prolymphocytes with nucleoli,... classification of mature T-cell and NK-cell neoplasms Leukemic / disseminated T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK-cell leukemia Adult T-cell leukemia/lymphoma Cutaneous Mycosis fungoides ´ Sezary syndrome Primary cutaneous anaplastic large cell lymphoma Lymphomatoid papulosis1 Other extranodal Extranodal NK/T cell lymphoma, nasal type Enteropathy-type T-cell... cases that do not display the features of LGL leukemia and must be classified as T-CLL The T-cell markers CD2, CD3, CD5, and CD7 are positive on immunophenotypic analysis CD4 and the T-cell receptor are positive in more than 50 % of cases, and CD8 is rarely detectable Cytogenetic analysis frequently demonstrates an inv(14) or aberrations of chromosome 8 (Figs 157, 1 58) Mantle Cell Lymphoma (MCL) This lymphomatous... enlargement of at least three lymph node regions C Same as A, plus anemia (Hb . ko¨n- nen B- und T-Zell-Lymphome unterschieden wer- den. B-Zell-Lymphome sind in Europa und Ame- rika ha¨ufiger, wa¨hrend die T-Zell-Lymphome in Asien u¨berwiegen. Unter Einbeziehung von mor- phologischen. lymphocytes of CLL have B-cell properties (B-CLL) in the majority of cases seen in Europe and America. The existence of a T-CLL is contro- versial. The mature-cell type of T-cell leukemia or NK-cell. Immunpha¨notyp oder gene- tisch-molekulargenetisches Profil nicht mo¨glich. B-, T- und NK-Zell-Neoplasien werden weiter in Vorstufen-(Precursor) und reife (mature) Er- krankungen unterteilt.